We hope to advance our understanding of the ecological control mechanisms which regulate the population sizes of the individual species that comprise the indigenous microflora of the large intestine. Earlier studies had shown that anaerobic continuous flow cultures mimic a large variety of in vivo interactions among species of the indigenous intestinal flora of the mouse, suggesting that the underlying control mechanisms may be similar in both habitats. We plan, therefore, to refine and extend the relevance and usefulness of anaerobic continuous flow cultures as in vitro models for the study of these mechanisms. This will be attempted by (1) changing the physical properties of the continuous flow culture apparatus, such as to increase the relative size of the adherent bacterial populations. We will further (2) attempt to study by a direct approach whether the ecological control mechanisms that regulate bacterial populations in vivo, are similar to those which have been found to operate in continuous flow cultures. (3) With the aid of mathematical models we will analyze and compare the efficiency of plasmid and bacteriophage transfer in continuous flow cultures of mouse indigenous large intestinal flora and in vivo. (4) A final major avenue of research will be to explore the possibility, that human large intestinal microflora may be maintained in its natural ecologic balance in gnotobiotic mice and in anaerobic continuous flow cultures. If the validity of these models can be established, they would considerably enhance the relevance of our study of ecologic control mechanisms to the control of human large intestinal flora.